• Radiation Oncology Journal
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• v.11 no.1
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• pp.43-50
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• 1993

We evaluated frequency and types of chromosomal aberrations by ionizing radiation in cancer patients treated with radiotherapy in our institution. Twenty-five patients with various types of carcinomas such as lung, uterine cervix, esophagus, rectum, head and neck and pancreatic cancers were studied immediately before and after external beam radiotherapy. The frequency of aberrant metaphase prior to treatment was $4.93{\%}$, which was higher than that of control group. Especially in lung cancer, the freuqency of aberrant metaphase was three times higher than control group. A comparison of chromosomal abnormalities observed before and after radiotherapy demonstrated that proportion of aberrant rnetaphases was significantly inreased to $22.13{\%}$. Major chromosomal aberrations like structural abnormalities showed remarkalbe increase from 65.45 to $88.45{\%}$ after the treatment. Also the numbers of chromosomal alterations per cell were increased by a factor of 6.5. Aberrations with two or more break points were more prominently increased, compared with aberrations with single break point. The number of chromosomal break points was noted to be higher than expected value in No.1, 3, 8 and 11 chromosomes and lower in No.13, 15, 17 and 21 chromosomes. Based on this study, we believe that the distribution of chromosomal breakage is related with gene and chromosomal rearrangement which could result in the development of cancers.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.162-162
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• 1993

제 3세대 platinum complex인 SKI 2053R에 의한 Salmonella typhimurium의 복귀변이빈도, CHL세포(Chinese Hamster Lung)에 대한 염색체이상 유발율 및 ddY계 마우스에서의 골수분화세포에 대한 염색체이상유발로 기인한 소핵의 빈도수를 관찰하여 SKI 2053R의 유전독성을 평가하였다. Salmonella typhimurium를 이용한 복귀돌연변이시험에서 SKI 2053R은 매우 경미한 정도의 돌연변이 유발성을 가지는 것으로 판단되며, 균주 특이적 돌연변이 유발성으로 보아 염기쌍치환형의 돌연변이를 유발하는 것으로 사료되며 포유류배양세포를 이용한 염색체이상실험에서 대사 활성 부재 및 존재하의 모든 시험 농도에서 10％ 이상의 염색체이상을 가진 세포가 관찰되었으며 염색체 상의 종류로는 염색분체형 교환 (cse)이 가장 많이 관찰되었다. 설치류를 이용한 소헥시험에서는 ddY계 마우스 골수세포의 분화과정에서 염색체이상을 유발하며, 다염성적혈구의 정염성적혈구에 대한 출현비율이 감소하는 결과로 볼때 방추체기능의 저해를 일으키는 것으로 판단된다. 그러므로 본 시험조건데 있어서 SKI 2053R은 소핵을 유발하는 물질로 결론지었다.

• Environmental Mutagens and Carcinogens
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• v.10 no.2
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• pp.85-92
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• 1990

The effects of aphidicolin (APC), 2`,3`-dideoxythymidine 5`-triphosphate (ddTTP), and novobiocin (NOV) on the frequencies of chromosome aberrations induced by ethyl methanesulfonate (EMS) or bleomycin (BLM) were examined in synchronized Chinese hamster ovary (CHO)-K$_1$ cells. The cells were synchronized by the thymidine double block method. APC, ddTTP and NOV alone did not affect the frequencies of chromosome aberrations. The cells in late G$_1$ and early S phases were sensitive to the induction of chromosome aberrations by EMS, wherase cells in G$_2$ phase were most sensitive to chromosme aberration by BLM.

• Environmental Analysis Health and Toxicology
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• v.24 no.1
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• pp.43-52
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• 2009

Fullerene의 유전독성을 평가하기 위하여 Chinese hamster유래의 난소유아세포(CHO-K1 cell)를 이용하여 직접법(-S9)과 대사활성화법(+S9 mix)의 염색체이상시험을 실시하였다. 시험물질은 1% CMC 나트륨염의 현탁액(1% CMC 용액)에 희석하여 조제하였다. 대사활성화를 시키지 않은 직접법의 염색체이상시험에서 24시간 투여군은 8단계의 농도(0.078, 0.156, 0.313, 0.625, 1.25, 2.5, 5, 10 mM)로 투여하여 실시하였다. 투여 농도 증가에 따른 염색체이상의 빈도가 증가하는 양상이 나타나지 않았다. 48시간의 투여군에서는 8단계의 농도(0.078, 0.156, 0.313, 0.625, 1.25, 2.5, 5, 10 mM)로 투여하여 실시하였는데 투여 농도 증가에 따른 염색체이상의 빈도가 증가하는 양상이 나타나지 않았다. 배수체의 염색체이상은 직접법에서 관찰되지 않았다. 대사활성화법을 이용하여 6시간 시험물질을 투여한 시험에 있어서는 8단계의 용량단계(0.078, 0.156, 0.313, 0.625, 1.25, 2.5, 5, 10mM)를 설정하였는데 투여 농도가 증가함에 따른 염색체이상빈도의 증가양상이 관찰되지 않았다. 이상의 결과를 종합할 때 본 시험물질은 본 시험 조건하에서 CHO-K1세포에서 대사활성화를 시켰을 때 염색체이상을 유발하지 않는 것으로 판단된다.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2002.11a
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• pp.77-77
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• 2002

본 연구는 체세포 및 체세포 핵이식란의 염색체 이상에 체세포의 계대의 영향성을 조사하고자 하였다. 한우 성축의 귀 조직으로 얻어진 세포를 공여세포를 체외성숙 후 제핵된 난자에 핵이식을 실시하였으며, 1.9kv/cm, 20$\mu\textrm{s}$/2times의 전기자극으로 융합후 5$\mu\textrm{g}$/ml의 ionomycin에서 4min, 1.9mM 6-DMAP에서 4h동안 배양함으로써 활성화를 유도하였다. 핵이식란은 CRlaa에서 4일간 배양 후 8 -cell단계에서 중기상의 유도를 위하여 상기 배양액 1ml당 0.05$\mu\textrm{g}$ colcemid에서 6-8시간 더 배양하였다. 이후, 6% Fetal bovine serum이 함유된 1% sodium citrate용액에 20분간 저장처리 후, methanol 5 : aceticacid 1 : distilled water 4로 1차, methanol 3: aceticacid 1 로 조성된 2차, methanol 4 : acetic acid 3 : distilled water 1의 3차고정액으로 1분간 재 침지시켰다. 고정 처리가 완료된 slide는 4% Giemsa용액으로 염색한 후 광학현미경 하에서 핵형 양상을 검경하였다. 체세포의 5계대에서는 684개의 spreads를 검경한 결과 염색체 수는 72%가 정상으로 60개이었고, 24%가 60개 이하였으며 4%가 60개 이상을 보였다. 10계대도 5계대와 비슷하여 71%가 정상, 26%가 60개 이하, 3%가 60개 이상이었고, 15계대에서는 55%가 정상이었고, 30%가 60개이하, 15%가 60개 이상을 보였다. 10계대 까지는 mixoploid의 비율의 변화가 없었으나 15계대에서 현저하게 늘어남을 볼 수 있었다. 또한 체외수정란과 핵이식란의 비교에서는 체외수정란은 250개의 spreads를 검경한 결과 염색체 수는 95.6%가 정상으로 60개이었고, 2.0%가 60개 이하, 2.4%가 60개 이상이었으나, 핵이식란은 204개를 검경하여 88%가 정상이었고, 4.9%가 60개이하, 7.1%가 60개 이상을 보임으로써, 핵이식란이 체외수정란에 비하여 염색체 이상의 비율이 높았다. 따라서 계대에 따라 체세포의 염색체이상의 비율이 상대적으로 증가하고, 체세포 핵이식에 따른 염색체 이상이 생길 수 있음을 알 수 있었다. (이 논문은 농림부 연구비에 의해 수행되었음)

• Radiation Oncology Journal
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• v.11 no.2
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• pp.233-240
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• 1993

Chromosomal aberration analysis, as a basis for biological radiation dosimetry, was performed for radiation dose ranges below 150 cGy. The yield, ratio of lymphocytes with dicentric and/or ring chromosomes, was 0, 0, 0.4, 0.5, 0.6, 0.8, 1.8, 5.5, 8.0, and $18.5\%$ for 0,5, 10, 15, 20, 25, 50, 75, 100 and 150 cGy, respectively. The Qdr, ratio of dicentric and ring chromosomes in total lymphocytes, was 0, 0, 0.004, 0.005, 0.006, 0.009, 0.018, 0.055, 0.084 and 0.207, respectively. The Qdr, ratio of dicentric and ring chromosomes in lymphocytes with aberration, was 1.0 for the radiation doses up to 75 cGy and 1.05 and 1.11 for 100 and 150 cGy, respectively. From the results, it seems possible to estimate radiation dose from Ydr when the exposure is 25 cGy or more. All the 5 radiation workers studied, with exposure much less than 1 mSv per month, had chromosomal aberrations. And acentric fragment pairs, in addition to dicentric and ring chromosomes, showed good dose response relationship and so may be useful for biological dosimetry for low dose radiation.

• Journal of Preventive Medicine and Public Health
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• v.22 no.1 s.25
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• pp.116-124
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• 1989

To assay the cytogenetic toxicity of $NiCl_2,\;K_2Cr_2O_7CdCl_2,\;and\;HgCl_2$, the frequencies of sister chromatid exchanges(SCEs) and chromosomal aberrations were observed in the metaphase chromosomes of the human lymphocytes which were cultured with above materials. The frequencies of SCEs are dose-dependently increased by all materials in this experiment. Chromosomal aberrations, especially gap and break, are increased by the nickel and chromic compounds, while not significantly increased by the cadmium and mercurial compounds. This results indicate the dose dependent relationship between the frequencies of SCEs and the concentrations of the heavy metals, but the increasing rates of the SCEs induced by the heavy metals are less sensitive than other mutagens or carcinogens which were confirmed.

• Journal of Genetic Medicine
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• v.8 no.1
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• pp.44-52
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• 2011

Purpose: Cytogenetic analysis of spontaneous abortions (SABs) provides valuable information to establish the causes of fetal loss, information that is essential to provide accurate reproductive and genetic counseling couples. Such analysis also provides information on the frequencies and types of chromosomal abnormalities and associated risks of recurrence. However, there have only been a few reports of chromosomal abnormalities in small samples of SABs in the Korean population. Here, we report the incidence and spectrum of chromosomal abnormalities for cases of 470 SAB in Korea. Material and Methods: Between 2005 and 2010, a total of 470 products of conception (POC) resulting from SABs were submitted to our laboratory for cytogenetic analysis from various medical sites in Korea. The incidences and types of specific chromosomal abnormalities were determined. The abnormalities were distinguished by gestational age at the time of SAB and by maternal age. Results: The frequency of chromosomal abnormalities in POCs was 54.3% (255/470), including 228 (89.3%) numerical and 27 (10.7%: 3 balanced and 24 unbalanced) structural abnormalities. Among the numerical abnormalities, trisomy was predominant (67.0%), followed by monosomy X (12.5%), polyploidy (8.2%), triple X (0.8%), and autosomal monosomy (0.8%). The overall sex ratio (male: female) among the 470 POCs with normal and abnormal karyotypes were 0.58 and 0.65, respectively. Trisomies were identified for each autosome, with the exceptions of 1, 3, and 19. Among the 171 autosomal trisomies, trisomy 16 was the most common (19.9%), followed by trisomy 22 (13.5%), trisomy 21 (12.3 %), trisomy 15 (9.9%), and trisomies 18 and 13 (5.3%). The frequency of chromosomal abnormalities decreased with gestational age and increased with maternal age, but only because of increases in trisomies and complex abnormalities. Conclusions: We have presented a large collection of cytogenetic data for SABs collected during the past 6 years and provided a database for prenatal genetic counseling of parents who have experienced SABs in Korea.

• Journal of Genetic Medicine
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• v.7 no.2
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• pp.111-118
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• 2010

Chromosomal microarray analysis (CMA) enables the genome-wide detection of submicroscopic chromosomal imbalances with greater precision and accuracy. In most other countries, CMA is now a commonly used clinical diagnostic test, replacing conventional cytogenetics or targeted detection such as FISH or PCR-based methods. Recently, some consensus statements have proposed utilization of CMA as a first-line test in patients with multiple congenital anomalies not specific to a well-delineated genetic syndrome, developmental delay/intellectual disability, or autism spectrum disorders. CMA can be used as an adjunct to conventional cytogenetics to identify chromosomal abnormalities observed in G-banding analysis in constitutional or acquired cases, leading to a more accurate and comprehensive assessment of chromosomal aberrations. Although CMA has distinct advantages, there are several limitations, including its inability to detect balanced chromosomal rearrangements and low-level mosaicism, its interpretation of copy number variants of uncertain clinical significance, and significantly higher costs. For these reasons, CMA is not currently a replacement for conventional cytogenetics in prenatal diagnosis. In clinical applications of CMA, knowledge and experience based on genetics and cytogenetics are required for data analysis and interpretation, and appropriate follow-up with genetic counseling is recommended.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.04a
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• pp.249-249
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• 1996

Gentamicin은 임상에서 많이 사용되는 aminoglycoside계 항생물질로서 세균의 세포막 단백질 합성을 억제하여 살균작용을 나타낸다. 최근 Gentamicin이 동물사료에 포함되거나 동물약품으로 많이 사용되어, 이를 복용한 식용가축에서의 잔류 량에 대한 인체유해성이 WHO/FAO 식품첨가물 전문가 협의회에서 논의되고 있다. Gentamicin의 육가공류의 잔류허용량 기준설정을 위한 독성 재평가의 일환으로 in vivo. in vitro 염색체이상시험을 실시하여 다음과 같은 결론을 얻었다. 1. 체외 염색체이상시험에서는 포유동물 배양세포인 chinese hamster lung cell을 배양하여 gentamicin sulfate 및 gentamicin을 최고 처리농도 5mg/$m\ell$부터 세포독성시험을 실시한 결과, 세포독성을 나타내지 않았다. 본 시험에서는 5mg/$m\ell$를 최고농도로 2.5, 1.25mg/$m\ell$의 3농도를 직접법 및 대사활성화법으로 각 농도당 2매의 플레이트씩 슬라이드를 제작, 결과를 판독한 결과, 직접법 및 대사활성화법 모두에서 전 농도 군에서 음성대조군과 같은 정도의 염색체이상을 유발하여 유전독성이 없음을 나타내었다. 2. 체내 염색체 이상시험에서는 ddY마우스를 이용하여 gentamicin sulfate의 LD$_{50}$의 1/2에 해당하는 200mg/kg을 최고농도로 gentamicin 과 gentamicin sulfate를 암수 각각 3마리씩 공비 2의 3농도로 투여한 후, 24시간째 골수세포의 염색체 표본을 제작하여 관찰한 결과, 세포독성 및 염색체 이상을 유발하지 않았다. 또한 동물약품으로 사용되는 치료용량 및 투약방법에 근거하여 10mg/kg 및 5, 2.5mg/kg을 1일 1회씩 4회 투여한 군에서도 암수에 상관없이 전 농도 군에서 염색체이상을 나타내지 않아 유전독성을 나타내지 않음을 관찰하였다.